PROJECT SUMMARY/ The mission of the Animal Modeling Core (AMC) is to provide research groups within the YCCEH and the larger scientific community access to the latest technologies for hematologic studies in animal models. In vivo studies allow researchers to ask questions about the function of molecules, cell populations, and tissues within the relevant spatial and temporal contexts. The YCCEH will continue to provide scientists training and facilitate research in mouse models of hematologic diseases. Importantly, the AMC will continue to develop and propagate the most innovative humanized mouse models for the study of human hematopoiesis and diseases thereof with the goal to overcome major shortcomings of current models. The AMC consists of two cores, the Humanized Mouse Core (HMC) and the Murine Stem Cell Transplantation Core (mSCTC). The Animal Modeling Core will be directed by Dr Richard Flavell, Sterling Professor of Immunobiology and co-directed by Dr. Stephanie Halene, Associate Professor and Acting Section Chief of Hematology. The HMC will offer expertise, technical assistance, and mice for human-into-mouse xenotransplantation studies. The mSCTC will offer training and technical assistance in the study of hematopoiesis and benign hematologic questions in mice. The Humanized Mouse Core will facilitate human-into-mouse xenotransplantation studies into immunodeficient mice. As a unique feature the Yale HMC will offer hematology researchers access to novel humanized immunodeficient mice optimized to support human hematopoietic stem cells, trilineage hematopoiesis, mature myeloid cells, red cells and platelets in circulation, and a functional human immune system. The Murine Stem Cell Transplantation Core will provide technical expertise in the study of hematologic questions in mice. The mSCTC will offer training and expertise for the study of hematopoiesis and hematologic diseases in mice using hematopoietic cell transplantation and functional assays. The Animal Modeling Core will be an integral part of the YCCEH. It will provide Hematology researchers with access to state-of-the-art technologies for in vivo studies of hematopoiesis and hematologic diseases. It will provide teaching, expertise, and resources in an economical way. Its cores will support basic science as well as translational studies, key to understanding and cure of hematologic diseases.